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Blockade of NF-kappaB improves cardiac function and survival without affecting inflammation in TNF-alpha-induced cardiomyopathy.

OBJECTIVE: NF-kappaB, a key transcription factor that regulates inflammatory processes, has been shown to be activated in the failing human heart with enhanced expression of proinflammatory cytokines. In the present study, we assessed the hypothesis that cardiotoxic effects of proinflammatory cytokines are mediated by the activation of NF-kappaB. METHODS: Transgenic mice with cardiac-specific overexpression of TNF-alpha were used as a model of cytokine-induced cardiomyopathy. To block the activation of NF-kappaB, transgenic mice (TG/p50(+/+)) were crossed with knockout mice in which the p50 subunit of NF-kappaB was disrupted (WT/p50(-/-)). RESULTS: The electrophoretic mobility shift assay demonstrated that NF-kappaB was activated in the myocardium of TG/p50(+/+) mice, while it was completely abolished in TG/p50(-/-) mice. Male TG mice died of congestive heart failure earlier than females, where the disruption of the p50 subunit significantly improved the survival. Compared with TG/p50(+/+) mice, TG/p50(-/-) mice showed a significant reduction of ventricular dilatation and hypertrophy with preserved fractional shortening. Although the myocardial expression of proinflammatory cytokines or infiltration of inflammatory cells was not affected, increased expression and activity of MMP-9 were significantly suppressed in TG/p50(-/-) mice. CONCLUSION: Blockade of NF-kappaB activation did not ameliorate myocardial inflammation but improved cardiac function and survival in male TNF-alpha TG mice. An inhibition of NF-kappaB may be a new therapeutic strategy for cardiac remodeling and heart failure, especially when proinflammatory cytokines are activated.

Animals↗

Long-term assessment and serial evaluation of cardiorespiratory exercise performance and cardiac function in patients with atrial switch operation for complete transposition.

BACKGROUND: At present, a considerable number of patients survive who underwent an atrial switch operation for correction of complete transposition. Our study aimed to assess their long-term exercise performance and the serial evolution of cardiac function. METHODS: We studied 22 patients 5 to 17 years after an atrial switch operation, and followed them serially for 3.5 +/- 2 years after the first evaluation. Cardiorespiratory exercise function was assessed by analysis of gas exhange and by determination of the ventilatory anaerobic threshold. Echocardiography was performed on all evaluations. RESULTS: All patients were in Class I of the classification of the New York Heart Association at all assessments. Ventilatory anaerobic threshold, however, was significantly lower than normal. It averaged 77.9% +/- 13.7 of the normal mean value at the initial evaluation, and remained stable when re-evaluated later (76.2 +/- 13.7%). At the initial study, the increase in oxygen uptake during graded exercise was below the 95% confidence limit in 6 of the patients, and was below this level in 10 patients at re-assessment. The subnormal values for oxygen uptake during submaximal exercise were associated with moderate to severe haemodynamic dysfunction. At echocardiography, 15 of 17 patients studied twice had mild to moderate right ventricular dilation and tricuspidregurgiation, which remained virtually the same at reasssesment. A stable sinus rhythm was initially present in 17 patients, and persisted in 15 patients during follow-up. CONCLUSION: At medium term follow-up, cardiorespiratory exercise performance remains stable in patients after atrial switch repair. Serial exercise testing appears useful, because in individual patients in the present study, a decreasing exercise tolerance correlated with development of haemodynamic sequels.

Adolescent↗

Doppler echocardiography and tissue Doppler imaging in the healthy rabbit: differences of cardiac function during awake and anaesthetised examination.

OBJECTIVE: In the past years, Doppler echocardiography has evolved into a commonly used technique. More recent sophisticated advances in imaging quality have substantially improved spatial and temporal resolution allowing the adaptation of this technique to small animal models, particularly in rabbits but even in mice. Recently, parameters obtained by Tissue Doppler Imaging (TDI) have been shown to be more independent of pre- and afterload than classic hemodynamic Doppler measurements. Exploration of animal models may require anaesthesia but there is only very little information on the effect of anaesthesia on echocardiographic parameters in rabbits. METHODS: We therefore performed Doppler-echocardiographic examinations of 20 wild-type New Zealand White rabbits in awake state and under light ketamine-xylazine anaesthesia. Special focus was put on the evaluation of global and regional left ventricular systolic and diastolic function using TDI and the myocardial performance index (Tei-index). RESULTS: Doppler-echocardiographic measurements including TDI in rabbits were feasible to assess cardiac morphology and function within a short examination time. There were some distinct changes of functional parameters during anaesthesia. Exemplary for systolic function, fractional shortening, cardiac output and systolic TDI velocity of the lateral wall decreased distinctly. Global left ventricular function measured by the Tei-index deteriorated. CONCLUSIONS: Doppler echocardiography and TDI can be performed easily, quickly and safely in the rabbit. Anaesthesia with the cardiodepressive ketamine-xylazine shows some distinct Doppler-echocardiographically measurable negative effects on cardiac function. Thus, echocardiography with less cardiodepressive anaesthetic regimes or even without anaesthesia after training of the animals should be considered as alternatives whenever possible.

Anesthesia↗

Cardiac functional and histopathologic findings in humans and mice with mucopolysaccharidosis type I: implications for assessment of therapeutic interventions in hurler syndrome.

Hurler syndrome (mucopolysaccharidosis type I [MPS I]) is a uniformly lethal autosomal recessive storage disease caused by absence of the enzyme alpha-l-iduronidase (IDUA), which is involved in lysosomal degradation of sulfated glycosaminoglycans (GAGs). Cardiomyopathy and valvar insufficiency occur as GAGs accumulate in the myocardium, spongiosa of cardiac valves, and myointima of coronary arteries. Here we report the functional, biochemical, and morphologic cardiac findings in the MPS I mouse. We compare the cardiac functional and histopathological findings in the mouse to human MPS I. In MPS I mice, we have noted aortic insufficiency, increased left ventricular size, and decreased ventricular function. Aortic and mitral valves are thickened and the aortic root is dilated. However, murine MPS I is not identical to human MPS I. Myointimal proliferation of epicardial coronary arteries is unique to human MPS I, whereas dilation of aortic root appears unique to murine MPS I. Despite the differences between murine and human MPS I, the murine model provides reliable in vivo outcome parameters, such as thickened and insufficient aortic valves and depressed cardiac function that can be followed to assess the impact of therapeutic interventions in preclinical studies in Hurler syndrome.

Animals↗

The effects of a new ultra-short-acting beta-adrenergic blocker, ONO-1101, on cardiac function during and after cardiopulmonary bypass.

The administration of an ultra-short-acting beta-adrenergic antagonist, esmolol, has been introduced as a novel method for beating-heart surgery. In the present study, a new ultra-short-acting beta-blocker, ONO-1101, was administered during cardiopulmonary bypass (CPB) to investigate its effects on cardiac function and hemodynamics. Nine adult mongrel dogs underwent 60 min of CPB during which they were given either ONO-1101 (ONO group; n = 4) or saline (control group; n = 5). In the ONO group, the hearts became flaccid enough for surgery to be performed without cardiac standstill within 10 min after the commencement of ONO-1101 with significant decreases in the heart rate, the preload recruitable stroke work (PRSW), and the slope of the end-systolic left ventricular pressure-volume relationship (Emax). The mean arterial pressure and systemic vascular resistance also decreased, but were maintained above 50 mmHg during CPB without catecholamine. These indices increased to the control group level 20 min after the discontinuation of ONO-1101. The serum concentration of ONO-1101 decreased from the maximum level of 121 +/- 15 microg/ml soon after infusion to 11 +/- 5 microg/ml within 30 min after discontinuation. These data suggest that ONO-1101 may be useful to enable beating-heart surgery to be performed without aortic cross-clamp as an ultra-short-acting beta-adrenergic blocker.

Adrenergic beta-Antagonists↗

Noninvasive ambulatory assessment of cardiac function in healthy men exposed to carbon monoxide during upper and lower body exercise.

Very little is known about the cardiovascular responses of exercising individuals when exposed to carbon monoxide (CO). Sixteen healthy nonsmoking men aged 18-29 years participated in the study. Using a combination of exposures to CO by breathing from a bag or in an environmental chamber, subjects performed a randomized sequence of brief (5 min) multi-level treadmill and hand-crank exercises on different days at less than 2% carboxyhemoglobin (COHb) and after attaining target levels of 5%, 10%, 15%, and 20% COHb. To assess cardiac function changes we employed noninvasive impedance cardiography (ICG) and three-lead electrocardiograms (ECG). The ICG was used to estimate cardiac output, stroke volume, heart rate, cardiac contractility, and time-to-peak ejection time. The ECG was used to assess myocardial irritability and ischemia, and changes in cardiac rhythm. The results showed that the cardiovascular system compensated for the reduced O2-carrying capacity of the blood by augmenting heart rate, cardiac contractility, and cardiac output for both upper-body and lower-body exercise. While this mechanism served well in submaximal exercise, the enhanced cardiovascular response to exercise was not without physiological costs because it began to fail at moderate levels of CO exposure and exercise. We concluded that young, apparently healthy men can perform submaximal upper and lower-body exercise without overt impairment of cardiovascular function after CO exposures attaining 20% COHb.

Adolescent↗

Cardiac function in hyperthyroidism.

It is accepted that thyroid hormones, thyroxine and tri-iodothyronine have direct inotropic and chronotropic effects on the heart. However, the mechanisms of manifestations are still uncertain. The following discusses and evaluates some of the theories regarding the interaction of these hormones with cardiac function.

Adult↗

Cardiac function during halothane anf fluroxene anesthesia expressed by systolic time intervals.

A non-invasive method of measuring the systolic time intervals (STI) during anesthesia is described. Using the ratio between the pre-ejection period and the left ventricular ejection time (PEP/LVET-ratio) as an expression of cardiac function, it is shown in 39 patients that thiopentone exerted a marked depression on the heart (increase in PEP/LVET-ratio). This depression was further aggravated by halothane, while fluroxene caused an improvement of PEP/LVET-ratio. In the immediate post-anesthetic period PEP/LVET-ratio almost reached control value after discontinuation of fluroxene in contrast to halothane, where an increased PEP/LVET-ratio (25%) still persisted. The changes were mainly due to a prolongation of PEP without any specific change in LVET. During the study, PEP/LVET-ratio showed a close correlation to the reciprocal value of the square of the pre-ejection period (1/PEP-2). STI form 27 volunteers were measured and compared to the values from the patients before anesthesia was induced. PEP and PEP/LVET-ratio were significantly shorter in the patient group.

Adolescent↗

Value of ventriculography in cardiac function and diagnosis.

The methods for calculating left ventricular volumes employing biplane angiocardiograms and the calculated parameters of left ventricular mass, pressure-volume diagrams, wall forces, compliance, and abnormally contracting segments are described. Examples of these calculations are given and the contributions to the assessment of cardiac function and diagnosis are discussed. Normal values and the alterations produced by volume overload, pressure overload, myocardial disease, and coronary artery disease are presented.

Angiocardiography↗

[The effect of chaihu qingxin yin on left cardiac function and T-cell subgroup in peripheral blood in children with viral myocarditis].

OBJECTIVE: To observe the effect of Caihu Qingxin Yin (CHQXY) in treating viral myocarditis. METHODS: CHQXY was used to treat 52 cases of acute viral myocarditis in children, compared with the routine method using energy mixture in 32 patients. RESULTS: (1) The total effective rate of 52 patients using CHQXY was 71.2% which was higher than that of the control group in 32 patients with 53.1%, Ridit analysis, P < 0.01. (2) Functional shortaxial shortening rate (FS) and ejecting fraction (EF) in CHQXY group were superior to those of the control group, P < 0.01. (3) CHQXY might modulate the immune function of T lymphocyte, enabled the CD3 and ratio of CD4/CD8 tended to normalize. CONCLUSION: CHQXY played an important role in the treatment of viral myocarditis with the mechanism of improving the left cardiac function and modulating celluar immune function.

Adolescent↗

Effect of methyldopa treatment on cardiac function and myocardial blood flow in mongrel dogs.

Administration of methyldopa (100 mg/kg, orally twice daily for a period of 3 days) to mongrel dogs produced significant reductions in blood pressure and heart rate. The hypotensive effect of the drug was due to a reduction in peripheral resistance. Methyldopa treatment also produced a significant decrease in coronary vascular resistance. Studies on the left ventricular function indicated that treatment with methyldopa does not compromise the ability of the myocardium to respond to an increased work load. Thus, the beneficial effect of this agent on the myocardial circulation, together with its lack of any detrimental effect on the cardiac function suggest that methyldopa may be an effective agent for the control of hypertension.

Animals↗

Depressed systolic and diastolic cardiac function after prolonged aerobic exercise in healthy subjects.

We studied 11 healthy untrained volunteers (aged 28.9 +/- 4.6 years) during 60 minutes of aerobic ergometric exercise with constant heart rates of 130 to 140 beats/minute. We found a continuous and significant decrease in systolic and diastolic pressure from 175 +/- 18/77 +/- 7 mmHg in the 5th minute to 144 +/- 14/68 +/- 6 mmHg in the 60th minute of exercise. Cardiac function and structure were assessed by M-mode echocardiography before exercise, after 5 minutes and after 60 minutes of exercise at comparable heart rates. The results demonstrated significant decreases in cardiac output, ejection fraction, and diastolic posterior wall velocity and an increase in total peripheral resistance after 60 minutes of exercise. We conclude that the decrease in blood pressure during long-term aerobic exercise in healthy untrained subjects might be at least influenced by a decrease in left ventricular filling and contractility, possibly indicating cardiac fatigue.

Adult↗

Relation between the initial portion of the signal-averaged QRS complex and cardiac function and infarct size in patients with myocardial infarction.

We analyzed signal-averaged electrocardiograms (ECG) obtained in 50 patients with recent myocardial infarction (RMI: 25 anterior and 25 inferior) and 20 normal subjects to determine the relationship between the initial portion of the signal-averaged QRS complex and cardiac function and infarct size. We examined (1) the root mean square voltage (RMS10-40, microV), (2) the integration (A10-40, microV.msec) at 10-msec intervals over the first 40 msec of the signal-averaged QRS complex, and (3) the intervals (T) of the magnitude of the signal-averaged ECG achieved at 10-microV intervals over the first 40 microV (T10-40, msec). The mean RMS10-40 (p < 0.01) and A10-40 (A10, p < 0.05; A20-40, p < 0.01) were significantly lower and the T10-40 (p < 0.01) was significantly longer in RMI patients than in normal subjects. The RMS10-40 (p < 0.01) and A10-40 (p < 0.05) were significantly lower and the T10-40 (T10.20, p < 0.01; T30.40, p < 0.05) was significantly longer in patients with anterior RMI patients than in patients with inferior RMI. The A30 was correlated with the ejection fraction and total creatine kinase (CK) release in all patients (r = 0.73, and -0.78, respectively, p < 0.001). These results suggest that the A30 may be an important predictor of ventricular dysfunction and infarct size in patients with RMI.

Adult↗

Identification of health damage due to alcohol abuse; importance of alterations in cardiac function and blood chemistries.

Like in any other disease, diagnosis of health damage caused by alcohol abuse can be established all the easier and sooner, the more results of medical examinations are taken into consideration simultaneously. Evidence is presented that a larger proportion (96.4%) of alcoholics suffer from compromised cardiac function (the classification function uses 6 variables out of the measured 21 than from disorders of liver function and the metabolism (87.7%) (the classification function uses 12 variables out of the 21). Taking into consideration all the 41 variables (using only 12) the power of discrimination is 99.2% (discriminant analysis).

Adult↗

[Venous flow velocity patterns and cardiac function studied by Doppler echocardiography].

To study the relations of central venous flow velocity (VFV) to cardiac pump function, hepatic venous flow velocity was recorded using Doppler echocardiography in six normal subjects and 47 patients with heart disease, of whom 28 had sinus rhythm and 19, atrial fibrillation. The area under the VFV profile during systole and diastole in a cardiac cycle was computed, and termed the VIs (systolic time-velocity integral) and VId (diastolic time-velocity integral), respectively. VIs was divided by the sum of VIs and VId [VIs/(VIs + VId)], and this was termed the VI ratio. The cardiac index (CI) was estimated by Doppler echocardiography. In normal subjects, the VFV pattern in a cardiac cycle was biphasic, the systolic VFV being dominant. In patients with atrial fibrillation, the systolic VFV was attenuated or absent, the diastolic VFV being dominant. The CI correlated well with the VI ratio (r = 0.80; p less than .001) in 14 patients with atrial fibrillation except for five patients with tricuspid regurgitation. Four patients in whom atrial fibrillation converted spontaneously to sinus rhythm showed an increase in the CI and the VI ratio according to the CI-VI ratio relationship. In patients with sinus rhythm, the CI tended to decrease as the VI ratio increased. In 15 patients who had a VI ratio of over 0.75, the CI correlated inversely with the VI ratio (r = -0.70; p less than 0.01). Three of four patients who had the VI ratio of 1.0 died of congestive heart failure. Although there was positive correlation between the CI and VI ratio in patients without effective atrial contraction, there was inverse correlation in patients with effective atrial contraction. It is suggested that the VI ratio could be a good indicator of cardiac pump function.

Adolescent↗

Applying principles of pharmacoeconomic evaluation to perflenapent emulsion, a new echocardiographic contrast agent for use in cardiac function testing.

A pharmacoeconomic evaluation was performed to determine the cost-effectiveness of perflenapent emulsion, a new contrast agent for use in echocardiography. A decision tree analysis was performed on data from the charts of 108 patients who had undergone stress echocardiography without contrast enhancement as part of a cardiac function or wall-motion study. An analysis of a theoretical cohort of patients was conducted to determine shifts in cost associated with enhancement of stress echocardiography with perflenapent emulsion. Outcome was determined by the point at which the clinician was able to determine a treatment course for the patient based on the diagnostic information given. Stress echocardiography without contrast was identified as the most cost-effective path in terms of a conclusive test. Perflenapent emulsion shows a positive cost impact in patients who have had an inconclusive stress echocardiogram without the use of a contrast agent. These results are supported by a sensitivity analysis across a wide range of pricing for perflenapent emulsion, a wide range of cost for a stress echocardiogram, and up to 99% efficacy of contrast-enhanced stress echocardiography.

Contrast Media↗